Recent studies of mouse models of Marfan syndrome (MFS) have shown that devising a successful treatment for such a congenital disease requires an integrated and unbiased understanding of the network of reciprocal interactions among extracellular, signaling and intracellular molecules. It follows that a systematic and multidisciplinary examination of a broad range of connective tissue disorders (CTDs) in the NIAMS mission area (skin, bone and muscle) should be fruitful in accelerating discoveries of treatment of these diseases. Computational systems biology is an emerging powerful strategy that, combined with traditional biochemical, cellular and genetic approaches, can reveal novel regulatory principles. The proposed this meeting is therefore to bring together basic, translational and clinical researchers in the areas of extracellular matrix biology, TGF-2 signaling, CTD and systems biology to: 1. Assess the current state of knowledge in the relevant fields for applying systems biology approach to delineate fundamental disease mechanisms of connective tissues. 2. Explore the advantage and limitations of combining computational modeling predictions with structure-based drug design and high-throughput screening of small molecules for targeting specific CTDs. 3. Identify needs in new technical infrastructures, support initiatives and funding opportunities (RFAs and PAs) that can facilitate interactions among basic and clinical scientists, promote interdisciplinary research and expedite translational applications. Such a meeting will be the first to be held that attempts to integrate the themes of CTD pathogenesis, TGF-2 basic biology, small-molecule therapeutics and systems biology. .